Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 69, Issue 12, Pages 1967-1995Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-011-0906-0
Keywords
Plasmodium falciparum; Malaria; Drug resistance; Chloroquine; Quinoline; PfCRT
Categories
Funding
- Australian National Health and Medical Research Council (NHMRC) [1007035, 520320]
- L'Oreal Australia For Women in Science programme
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The prevention and treatment of malaria is heavily dependent on antimalarial drugs. However, beginning with the emergence of chloroquine (CQ)-resistant Plasmodium falciparum parasites 50 years ago, efforts to control the disease have been thwarted by failed or failing drugs. Mutations in the parasite's 'chloroquine resistance transporter' (PfCRT) are the primary cause of CQ resistance. Furthermore, changes in PfCRT (and in several other transport proteins) are associated with decreases or increases in the parasite's susceptibility to a number of other antimalarial drugs. Here, we review recent advances in our understanding of CQ resistance and discuss these in the broader context of the parasite's susceptibilities to other quinolines and related drugs. We suggest that PfCRT can be viewed both as a 'multidrug-resistance carrier' and as a drug target, and that the quinoline-resistance mechanism is a potential 'Achilles' heel' of the parasite. We examine a number of the antimalarial strategies currently undergoing development that are designed to exploit the resistance mechanism, including relatively simple measures, such as alternative CQ dosages, as well as new drugs that either circumvent the resistance mechanism or target it directly.
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